Pegcetacoplan Slows GA Progression, Doesn’t Impact Visual Acuity in Real-World Study

New research offers a nuanced perspective on pegcetacoplan, a recently approved treatment for geographic atrophy (GA) secondary to age-related macular degeneration (AMD). While the drug demonstrably slows the progression of this vision-threatening condition, a real-world analysis published in Vision indicates it does not appear to halt the decline in visual acuity.

Geographic atrophy is an advanced form of dry AMD, characterized by the gradual breakdown of cells in the macula, the central part of the retina responsible for sharp, central vision. As these cells deteriorate, patients experience progressive vision loss. Approximately 25% of GA cases without neovascular AMD (nAMD) at baseline are diagnosed with nAMD within three years, and roughly a quarter of new nAMD diagnoses occur alongside existing GA, highlighting the frequent coexistence of these conditions.

The study, conducted by researchers at Retina Consultants of Texas, retrospectively examined the electronic health records of 168 eyes from 110 patients diagnosed with GA due to AMD. Data were collected for five years prior to initiating pegcetacoplan treatment and for nine months following treatment initiation. Researchers utilized spectral domain OCT imaging and an automated AI algorithm to measure the rate of retinal pigment epithelium (RPE) and ellipsoid zone (EZ) depletion – key indicators of GA progression.

The analysis revealed a significant slowing of both RPE and EZ depletion rates after treatment. The square root depletion rate for the RPE decreased from 0.25 mm per year to 0.096 mm per year, while the rate for the EZ decreased from 0.26 mm per year to 0.049 mm per year. These findings suggest that pegcetacoplan effectively targets the underlying disease process, reducing the rate at which retinal cells are lost.

However, despite this anatomical benefit, the study found no corresponding improvement in visual acuity. Average best-corrected visual acuity (BCVA) worsened at a rate of 0.05 logMAR per year both before and after starting pegcetacoplan injections. This suggests that while the drug can slow the structural damage caused by GA, it does not prevent the functional consequences – the loss of vision – that patients experience.

Further analysis revealed that approximately 45.2% of the eyes studied had both GA and neovascular AMD at baseline. A substantial 77.7% exhibited foveal involvement, meaning the GA affected the central macula, which is critical for detailed vision. The researchers noted that the real-world findings align with the results observed in the phase 3 clinical trials of pegcetacoplan.

“While the follow-up interval in the current study was limited, no appreciable change in VA trajectory was observed following pegcetacoplan initiation,” the researchers wrote. “Longer-term data following pegcetacoplan initiation and larger datasets may be useful to more completely understand the impact of pegcetacoplan in clinical practice.”

A separate study, published in the American Journal of Ophthalmology and involving 154 eyes injected with pegcetacoplan, with follow-up data available for 103 eyes, corroborated these findings. This real-world study demonstrated a 37% decrease in GA growth rate, but also observed a significant loss of BCVA. Notably, eyes with prior anti-VEGF therapy were more likely to develop exudation, or fluid leakage, within the retina.

The findings from both studies underscore the complex nature of GA and the limitations of current treatments. While pegcetacoplan represents a significant advance in the management of this condition, it is not a cure. Patients should have realistic expectations about the potential benefits and limitations of the therapy.

Another study, published in the American Academy of Ophthalmology’s EyeNet, highlights that two years of pegcetacoplan injections did not prevent the loss of best-corrected visual acuity, reading ability, patient-reported visual functioning, or threshold sensitivity. This reinforces the idea that slowing GA progression does not automatically translate to preserved vision.

The availability of complement inhibitors like pegcetacoplan and avacincaptad pegol has been eagerly anticipated by the eyecare community. While clinical trials showed promise in slowing GA lesion growth, concerns regarding safety, such as retinal occlusive vasculitis and vision loss, have prompted careful monitoring of real-world outcomes. The current data suggest that pegcetacoplan performs as expected based on clinical trial results, offering a benefit in slowing disease progression without necessarily preventing vision loss.

Further research is needed to fully understand the long-term effects of pegcetacoplan, particularly in patients with coexisting nAMD and those who have previously received anti-VEGF therapy. Continued monitoring and data collection will be crucial to optimizing treatment strategies and improving outcomes for individuals affected by geographic atrophy.